Divergent mechanisms for trophic actions of estrogens in the brain and peripheral tissues

► Estrogens have trophic effects in the body and brain via different receptor targets. ► Trophic actions in uterus and mammary tumors occur through estrogen receptor (ER) α. ► Trophic actions in the hippocampus for affect and learning occur through ERβ. ► ERβ actions can be rapid, occur outside the nucleus, and involve histone signaling. ► This review challenges the maxim that steroids have slow, long-term, distal effects.